Multicomponent Reactions (MCRs) are one-pot reactions, in which three or more starting materials react to form a product, where basically all or most of the atoms contribute to the newly formed product. Speed, diversity, efficiency, atom-economy and environmental friendliness are some of the notable features of this class of reactions. The most important MCRs are the isocyanide-based reactions such as the Passerini three-component reaction and the Ugi four-component reaction. Moreover, a variety of heterocycles can be constructed using the MCR strategy, where zwitterionic intermediates are generated by the addition of nucleophile to activated C—C multiple bonds followed by their interception with a third component.
The synthetic utility of arynes in MCRs has been recently significant as this method allows a straightforward access to various multisubstituted arenes of structural complexity and diversity. The initial reports on aryne MCRs utilize the anionic nucleophiles as the nucleophilic trigger. Arynes are highly electrophilic reactive intermediates, which have been extensively utilized in various carbon-carbon and carbon-heteroatom bond-forming reactions. Arynes have been employed for the construction of multisubstituted arenes of structural diversity and complexity. This kinetically unstable intermediate can react with a wide variety of anionic and uncharged nucleophiles leading to a direct approach to access 1,2-disubstituted arenes, which are structural fragments in many natural compounds as well as biologically active compounds.
Hence the process for the preparation of these compounds and newer forms is an area of continuous research. One of the important aspects of aryne chemistry is multicomponent reaction, which mainly include the initial addition of nucleophiles to arynes and subsequent trapping of the aryl anion intermediate with electrophiles. If the nucleophile and electrophile do not belong to the same molecule, the overall process is a unique three-component coupling, where the aryne is inserted between the other two coupling partners. This versatile transition-metal-free methodology has been applied to the synthesis of valuable heterocycles and in natural product synthesis.

Article titled “Arynes in a Three-Component Coupling Reaction: Straightforward Synthesis of Benzoannulated Iminofurans” by Hiroto Yoshida et al. published in Angewandte Chemie International Edition, 2004, 43 (30), pages 3935-3938 reports a variety of benzoannulated iminofurans obtained from an aryne, an isocyanide, and an aldehyde in modest to high yields.

Yoshida, Kunai and coworkers employed isocyanides as the neutral nucleophile source and they reported an efficient MCR involving arynes, isocyanides and aldehydes leading to the formation of benzannulated iminofuran derivatives. Interestingly, however, the synthetic utility of N-heterocycles as nucleophiles in aryne MCRs has got only limited attention.
Article titled “Three-Component Coupling of Arynes, Aminosilanes, and Aldehydes” by Hiroto Yoshida et al. published in Organic Letters, 2007, 9 (17), pp 3367-3370 reports a three-component coupling of arynes, aminosilanes, and aldehydes enables diverse amino and hydroxymethyl groups to be incorporated directly into 1,2-positions of aromatic rings. The reaction carried out in presence of KF and 18-Crown-6 in THF solvent.
Article titled “Arynes in Transition-Metal-Free Multicomponent Coupling Reactions” by S Bhojgude et al. published in Angewandte Chemie International Edition, 2012, 51 (7), pages 1520-1522 reports the multicomponent reactions involving arynes offer direct access to unusual heterocyclic scaffolds and 1,2-disubstituted arenes. The transition-metal-free multicomponent coupling reactions between arynes, isocyanides and terminal alkynes.
Article titled “Strategies for Heterocyclic Construction via Novel Multicomponent Reactions Based on Isocyanides and Nucleophilic Carbenes” by Vijay Nair et al published in Acc. Chem. Res., 2003, 36 (12), pp 899-907 reports that rea of multicomponent reactions (MCRs) involving zwitterionic species generated by the addition of isocyanides and nucleophilic carbenes such as dimethoxycarbene and N-heterocyclic carbenes to activated alkynes. The strategy employed encompasses the interception of 1:1 zwitterionic species, generated in situ with a wide range of electrophiles.
Article titled “Transition-Metal-Free Multicomponent Reactions Involving Arynes, N-Heterocycles, and Isatins” by Anup Bhunia et al. in Angewandte Chemie, 2013, 125 (38), pages 10224-10227 reports transition metal free multicomponent reaction involving arynes, N-heterocycles and N-substituted isatins, when the isoquinoline is used as the nucleophile, the reaction furnishes the spirooxazino isoquinoline analogues of Formula (I) and when pyridine is used as nucleophilic trigger, the reaction affords indolin 2-one analogues, wherein the reaction is carried out under mild condition in presence of KF and [18]-crown-6 in suitable organic solvents.
Multicomponent reaction using aryne is known in the art, but utilizing N-heteroaromatic compounds as the nucleophilic trigger is very rare.